This research will be done primarily in Ibadan, Nigeria at the University of Ibadan and in Kingston, Jamaica at the University of the West Indies in collaboration with Richard Cooper, as an extension of NIH Grant No. R01HL053353, 6/15/09-4/30/14. Hemoglobinopathies are the most common monogenic disorders in the world. Recent findings indicate that genetic variation associated with fetal hemoglobin (HbF) levels strongly influences severity in patients with sickle cell disease (SCD) and 2-thalassemia, offering potential insights into novel therapies. Despite the high prevalence of SCD in West Africa, relatively little research has been conducted in this region utilizing modern genomic technology. In addition, life expectancy of patients with SCD has been greatly extended in industrialized countries, in part as a result of improved medical management. However management of SCD and development of comprehensive life-course care has lagged behind in Africa. A South-South collaboration between Jamaica and Nigeria provides an excellent opportunity to transfer advances in clinical care for SCD that are appropriate for low resources countries. In this project we propose to build on two decades of collaborative research in the West African diaspora to link investigators in Nigeria and Jamaica with institutions in North America to build research capacity in SCD and advance our understanding of the genetic influences on severity. We further propose to enhance the clinical SCD activities at the collaborating institution in Nigeria, provide training for our Nigerian collaborator, and create a model for outcomes and management research in the region. The specific aims of this project are 1) to establish a research collaboration between investigators at the University College Hospital (UCH), Ibadan, Nigeria, the University of the West Indies (UWI), Mona, Kingston, Jamaica, and Loyola Medical School, Chicago, USA to study genes which modify severity and clinical outcomes in SCD; 2) to share the clinical expertise from the 40-year experience of the Sickle Cell Unit, UWI, Mona to enhance the patient care of SCD at UCH, Ibadan; 3) to collect DNA and phenotypic information on 300 homozygous sickle cell patients from Ibadan; and 4) to perform association tests for and HbF levels and clinical severity with loci previously shown to modify HbF expression. We anticipate that this project will provide pilot data for a large-scale study of the clinical and genetic aspects of SCD in the Nigerian context. The samples and clinical data base can serve as the basis for future research, including extensive re-sequencing of key loci influencing HbF to identify causal mutations.